The necessity to meet the rising global demand for mobility and energy supply and, at the same time, the urgency to minimize the carbon footprint, leads to the challenging scientific question of the fatigue resistance of emerging eco-efficient concretes. Since existing knowledge of the traditional Portland-clinker-based binders is largely empirical, it cannot be directly transferred to new binder systems, exhibiting complex chemical and mechanical interactions within the heterogeneous material structure. In contrast to the well-established insight into the high-cycle fatigue of metals, a complete understanding of the fatigue degradation processes in concretes is still lacking. In this research, we are committed to pioneering an innovative approach that establishes a universally applicable link between the chemical/microstructural composition of novel concrete materials and their fatigue resistance. To create an interdisciplinary methodology for the scientific analysis of fatigue-resistant eco-efficient concretes, complementary competences of a multidisciplinary research team will be combined in a concerted application of physico-chemical modeling approaches of hydration processes and advanced methods of multiscale and multifield computational mechanics supported by machine learning and accompanied by a rigorous experimental validation program. The developed coherent methodical framework will include innovative theoretical and numerical as well as tailored experimental approaches covering all relevant spatial and temporal scales to enable realistic predictions of the fatigue behavior of existing and future eco-efficient concrete formulations. This is necessary to give design engineers confidence in the new materials, and to enable design concepts, optimally satisfying requirements for sustainable, economical, and reliable future transportation and energy infrastructure.